One of the changes occurring in modern society is the progressive ageing of population. Such a phenomenon is accompanied by the onset of degenerative pathologies involving difficulties in coordination and in swallowing the traditional oral forms such as tablets or capsules. Said problems are also present, in other population groups, such as children.
On the other hand, the need for solid pharmaceutical forms capable of making the medicament available within a short time from the administration is particularly felt even for those patients who do not have any swallowing problems.
In some fields of therapy, such as that relating analgesia, fast acting medicaments to be administered by the oral route are nowadays particularly required.
The conventional solution to such a problem is usually provided by water-soluble effervescent tablets.
In this case, the patient ingests the aqueous solution resulting from the disintegration of the tablet in water so that the active ingredient already dissolved or dispersed in water is in a highly bio-available form.
A number of methods for the preparation of granulates suitable to the preparation of effervescent tablets are known. One of said methods, so-called "single phase", consists in keeping in suspension, in an air stream, the effervescent mixture and optionally any excipients and in granulating said mixture using water and/or a binding polymer. The mass, after the granulation phase, is dried, sieved and collected in a single operation.
The effervescent tablets, however, in order to be administered, have to be dispersed in a carrier, since they cannot be ingested directly. This is in many cases, a restriction to the use of such a pharmaceutical formulation for the above mentioned population groups.
Therefore, tablets that dissolve in the mouth, that are to the oral or sublingual administration, have been suggested.
The buccal tablets are intended for disintegration in the mouth, the patient placing them in the buccal cavity, on the tongue or between cheeks and gums, thereby allowing a slow dissolution, which usually requires 30 to 60 minutes (E. Rotteglia "Compresse farmaceutiche", Societa Editoriale Farmaceutica, Milan, Italy, 1966).
On the contrary, sublingual tablets are intended to be placed under the tongue, wherein the active substance can be directly absorbed through the mucosa. These forms are provided with slow-disintegration formulations as well (E. Rotteglia, ibid. and S. Casadio, Tecnologia Farmaceutica II Ed., Cisalpina Goliardica, Milan, Italy).
This type of prolonged release is hardly suitable for formulating active ingredients, such as analgesics, which have to exert an immediate effect.
Such a requirement can be met by freeze-dried sublingual tablets such as those prepared according to the Zydis patented (R) procedure for creating a rapidly dissolving oral formulation. Zydis is a registered trademark of the R.P. Scherer Company (Manufacturing Chemist, 36-37, February 1990).
However, such formulations are very expensive and require sophisticated technologies and methods from the production point of view. These products are substantially freeze-dried products, the pharmaceutical formulation being therefore difficult to handle (due to its high friability and fragility) and requiring specific packaging. A problem with freeze-dried sublingual tablet formulations is the impossibility to effect any taste-masking on the active ingredient.
WO 8808298 (Fuisz Technologies, Nov. 3, 1988) discloses rapid-dissolution pharmaceutical compositions in which the active ingredient is included in a water-soluble carrier obtained through a specific preparation process which requires a specific, expensive plant. Moreover, the resulting compositions exhibit friability problems and must always be handled and packed with particular precautions (use of dehydrating agents, humidity-tight packages, controlled-humidity work environment and so on).
EP-A-494972 (Cima Labs Inc.; Jul. 22, 1992) describes effervescent tablets suitable to the direct oral administration, i.e. without a previous development of the effervescence in water, consisting of microcapsules containing the active ingredients and an amount of effervescent agents sufficient to promote the release of the microgranules when ingested and to give a "fizzing" sensation when in contact with the buccal mucosa of the patient.
The amount of effervescent agents, typically citric acid and a carbonate or a bicarbonate, ranges from 5 to 50% by weight compared with the composition total weight, preferably from 15 to 30%. Dissolution times in the mouth range from 30 seconds to 5-7 minutes.
In this case also, notwithstanding the presence of amounts of effervescent agents lower than in conventional formulations (60% by weight compared with the composition total), the typical cautions used for the effervescent tablets should be taken.
Further drawbacks are the friability of the tablets and the use of microcapsules. In fact, the preparation technique described in EP-A-494972 does not envisage the humid granulation, i.e. using a solvent, but the direct mixing of the powders and the subsequent compression. Such a preparation technique yields tablets having friability values higher than those involving the humid granulation of the mixture to be pressed.